Restraint stress, foot shock and corticosterone differentially alter autophagy in the rat hippocampus, basolateral amygdala and prefrontal cortex

Abstract

Abstract Autophagy is a conserved lysosomal degradation process that has recently been found to be associated with stress-related psychological diseases. However, previous studies have yielded inconsistent results regarding the effects of various stress patterns on autophagy in different brain regions. This discrepancy may arise from differences in autophagy flux across nuclei, the type of stress experienced, and the timing of autophagy assessment after stress exposure. In this study, we assessed autophagy flux in the rat hippocampus (HPC), medial prefrontal cortex (mPFC), and basal lateral amygdala (BLA) by quantifying protein levels of p-ULK1, LC3-I, LC3-II, and p62 via Western blot analysis at 15 min, 30 min, and 60 min following various stress paradigms: restraint stress, foot shock, single corticosterone injection, and chronic corticosterone treatment. We found that: 1) hippocampal autophagy decreased within 1 hour of restraint stress, foot shock, and corticosterone injection, except for a transient increase at 30 min after restraint stress; 2) autophagy increased 1 hour after restraint stress and corticosterone injection but decreased 1 hour after foot shock in mPFC,; 3) In BLA, autophagy increased 1 hour after foot shock and corticosterone injection but decreased 1 hour after restraint stress; 4) Chronic corticosterone increased autophagy in mPFC and BLA but had no effects in HPC. These findings reveal temporally and spatially distinct autophagy flux patterns in the brain within 1 hour of stress exposure. Such dichotomous responses may contribute to the development of stress-related psychological disorders.